Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro

Abstract

Mannose-binding lectin (MBL), a pattern-recognition molecule in serum, recognizes specific hexose sugars rich in mannose and N-acetylglucosamine on bacterium, yeasts, viruses as well as apoptotic cells. It has been well-identified that MBL has antiviral effects via binding to seasonal influenza H1 and H3 subtype viruses. Influenza A (H7N9) virus, a novel reassortant virus to human population, possesses the surface hemagglutinin (HA) and neuraminidase (NA) genes from duck and wild-bird influenza viruses and internal genes from poultry H9N2 viruses. As of Dec 7th, 2014, a total of 467 human infections and 183 fatal cases have been identified. Here, recombinant human (rh) MBL was tested for its binding and effects on hemagglutination inhibition (HI) and NA activity inhibition (NAI) of avian H7N9, H9N2 and human H3N2 viruses. We discovered that rhMBL exhibited a strong binding to H7N9 virus as human H3N2 did at high virus titers. However, it performed a significantly weaker HI activity effect on H7N9 comparing to those of H3N2 and H9N2, even at a much higher concentration (3.67 ± 0.33 vs. 0.026 ± 0.001 and 0.083 ± 0.02 μg/mL, respectively). Similarly, minor NAI effect of rhMBL, even at up to 10 μg/mL, was found on H7N9 virus while it displayed significant effects on both H3N2 and H9N2 at a lowest concentration of 0.0807 ± 0.009 and 0.0625 μg/mL, respectively. The HI and NAI effects of rhMBL were calcium-dependent and mediated by lectin domain. Our findings suggest that MBL, the host innate molecule, has differential interference effects with human and avian influenza virus and limited antiviral effect against H7N9 virus.

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection

“…However, this needs to be balanced as the antiviral function of MBL may vary among different strains of influenza viruses, depending on the number of potential glycosylation sites on the viral haemagglutinin globular domain. MBL has been shown to inhibit influenza A seasonal H3N2 and seasonal H1N1 viruses through direct neutralization, indirect opsonization, and complement activation, but limited antiviral effect against H7N9 virus [18]. In contrast, MBL can bind to influenza A(H1N1)pdm09 virus but fails to inhibit its infection in human lung epithelial cell line.…”

Influenza virus N-linked glycosylation and innate immunity

“…As noted above, reduced morbidity, mortality, and viral lung titers in mice and ferrets were observed with A(H1N1) and A(H3N2) IAV as the level of HA glycosylation increased [96–100]. Viruses that have low levels of glycosylation, such as the pandemic 1918 A(H1N1), 1957 A(H2N2), 1968 A(H3N2), and 2009 A(H1N1)pdm09 strains [96,98,101–106] and the zoonotic A(H5N1) [94,107–109] and A(H7N9) [110] strains, are relatively resistant to neutralization by SP-D and MBL in animal models, while highly glycosylated viruses are typically more susceptible [98,111–113].…”

Antiviral activities of atractylon from Atractylodis Rhizoma

“…The histological changes in the lungs of the mice were noted with the aggravation of the infection. After IAV challenge, lung index was obviously increased compared to the normal control group ( Table III ) since IAV causes red blood cell agglutination and monocytic infiltration, resulting in interstitial pneumonia and progressive lung weight ( 29 , 30 ). The IAV-induced lung injury characterized by the presence of interstitial edema, hemorrhage and infiltration of inflammatory cells could also be observed in the tissues ( Fig.…”